Inosine and D-Mannose Secreted by Drug-Resistant Klebsiella pneumoniae Affect Viability of Lung Epithelial Cells

Molecules

Lixin Xie¹  Wei Guan¹  Yuhan Zhang¹  Shaoyan Gu¹  Jiang Wang¹  Qingzhong Wang²  Yuting Tang³  Jiaqi Shen³  Lu Zhang³  Wenxuan Xiao³  Farui Shu³  Ziwei Zhou³ 

[1] College of Pulmonary and Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing 100853, China;Shanghai Centre for Clinical Laboratory, Shanghai 200126, China;State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200437, China;

关键词: Klebsiella pneumoniae;    drug resistance;    A549;    metabolomics;    inosine;    D-mannose;   

DOI  :  10.3390/molecules27092994

来源: DOAJ

【 摘 要 】

The antibiotic resistance rates of Klebsiella pneumoniae have been steadily increasing in recent years. Nevertheless, the metabolic features of the drug-resistant Klebsiella pneumoniae and its associated benefits for bacterial pathogenicity are far from expounded. This study aims to unravel the unique physiological and metabolic properties specific to drug-resistant K. pneumoniae. Using scanning electron microscopy (SEM), we observed a thicker extracellular mucus layer around a drug-resistant K. pneumonia strain (Kp-R) than a drug-sensitive K. pneumonia strain (Kp-S). Kp-R also produced more capsular polysaccharide (CPS) and biofilm, and appeared to have a significant competitive advantage when co-cultured with Kp-S. Moreover, Kp-R was easier to adhere to and invade A549 epithelial cells than Kp-S but caused less cell-viability damage according to cell counting kit-8 (CCK-8) tests. Immunofluorescence revealed that both Kp-R and Kp-S infection destroyed the tight junctions and F-actin of epithelial cells, while the damage caused by Kp-S was more severe than Kp-R. We detected the extracellular metabolites secreted by the two strains with UHPLC-Q-TOF MS to explore the critical secretion products. We identified 16 predominant compounds that were differentially expressed. Among them, inosine increased the viability of epithelial cells in a dose-dependent manner, and an A_2AR antagonist can abolish such enhancement. D-mannose, which was secreted less in Kp-R, inhibited the viability of A549 cells in the range of low doses. These findings provide potential targets and research strategies for preventing and treating drug-resistant K. pneumoniae infections.

【 授权许可】

Unknown